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Mini II > Pre-Cancer: Molecular Basis of Cancer > Flashcards

Pre-Cancer: Molecular Basis of Cancer Flashcards

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1
Q

what is the pre-cancerous condition of the stomach that leads to gastric adenocarcinoma?

A

Atrophic Gastritis of pernicious anemia

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2
Q

what pre-cancerous condition leads to melanoma in the skin?

A

dysplastic nevus

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3
Q

Barrett esophagus leads to?

A

Adenocarcinoma of esophagus

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4
Q

H. pylori infection can lead to?

A 
Adenocarcinoma of stomach
MALT lymphoma (MALToma)
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5
Q

Chronic ulcerative colitis can lead to?

A

Adenocarcinoma of colon

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6
Q

Hep B, Hep C, cirrhosis can all lead to?

A

Hepatocellular carcinoma

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7
Q

Atypical ductal hyperplasia can lead to?

A

Adenocarcinoma of boob

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8
Q

Lichen sclerosis can lead to?

A

Squamous cell carcinoma of Vulva

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9
Q

Chronic cystitis can lead to?

A

Urothelial carcinoma of urinary bladder

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10
Q

RB1- predisposition for?

A

Retinoblastoma

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11
Q

p53- predisposition for?

A

Li-Fraumeni syndrome (multiple tumors)

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12
Q

APC- predisposition for?

A

Familial adenomatous polyposis

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13
Q

NF1, NF2- predisposition for?

A 
Neurofibromatosis 1
Neurofibromatosis 2 (bilateral Schwannoma of acoustic nerve)
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14
Q

BRCA1, BRCA2- predisposition for?

A

Breast cancer, Ovarian cancer

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15
Q

MEN1, RET- predisposition for?

A

Multiple endocrine neoplasia 1 and 2

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16
Q

p16INK4A (CDKN2A)- predisposition for?

A

Melanoma

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17
Q

MSH2, MLH1, MSH6- predisposition for?

A

Hereditary non-polyposis colon cancer

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18
Q

Retinoblastoma

what is the two hit theory?
What is the MOA behind Retinoblastoma?
What are the clinical signs?
Predisposition for ___ in adolescents?

A

Loss of RB tumor suppressor gene on chromo 13. It is a malignancy of eye in children

“two-hit theory”
- one gene inactivated in germ cells, the other after birth.

  • White pupillary reflex & visual loss
  • Predisposition for Osteosarcoma in adolescence
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19
Q

Familial Adenomatous Polyposis (FAP). Leads to development of what?

A

Inactivation of APC tumor suppressor gene

Development of Colorectal carcinoma from malignant transformation of polyps by age 30

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20
Q

Multiple Endocrine Neoplasia

A

MEN II –> mutation of rET protooncogene

familial occurence is combination:

  1. medullary thyroid carcinoma
  2. bilateral pheochromocytoma
  3. hyperparathyroidism due to hyperplasia or tumor
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21
Q

Herditary Non-polyposis Colorectal Cancer (HNPCC)

A
  • familial clustering of cancers at several sites
  • colon cancers at young age (often R sided)
  • DNA mismatch repair (MSH2 and MLH1 and MSH6)

“Cluster of genes, cluster of cancer”

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22
Q

Xeroderma pigmentosum

A

Mutated Nucleotide Excision Repair (NER) enzymes.

Defect in DNA repair of UV damaged skin

Predisposition to multiple skin cancers- Basal cell carcinoma, squamous cell carcinoma, malignant melanoma

excessive photosensitivity and 2000x increase in skin cancers

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23
Q

Ataxia-telangiectasia

A

Mutated ATM gene which usually repairs DNA damaged by ionizing radiation

Predisposition to lymphoma, leukemia, breast cancer

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24
Q

Bloom’s syndrome

A

Mutated BLM gene. DNA helicase family

Predisposition to lymphoma, leukemia

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25
Fanconi's anemia
Mutated FAC gene Predisposition to lymphoma, leukemia and bone marrow aplasia
26
Breast/ovarian cancer
Inactivated BRCA1, BRCA2 genes
27
Familial melanoma
Mutated p16INK4A gene
28
Overexpression of PDGFB gene or TGF-alpha
Astrocytoma
29
Overexpression of HST1 gene
Osteosarcoma
30
Amplification of FGF3 gene
Stomach Bladder Breast Melanoma
31
Overexpression of HGF
Hepatocellular carcinoma | Thyroid cancer
32
amplification of ERBB2 (HER) causes ____ cancer
Breast carcinoma
33
Point mutation of RET causes ________ cancers
Multiple endocrine neoplasia 2A and B and Familial medullary thyroid carcinomas
34
Translocation on ABL gene
CHRONIC myelogenous leukemia
35
Point mutation at ABL gene
ACUTE lymphoblastic leukemia
36
Point mutation at BRAF gene
Melanoma
37
What causes burkitt lymphoma?
translocaiton on MYC
38
What causes neuroblastoma?
Amplification of N-MYC
39
Point mutation in ____ gene is found in 15-20% of all cancers
RAS
40
t(9;22)
Chronic myeloid leukemia (CML) ABL, BCR genes- forms Philadelphia chromosome
41
t(8;14)
Burkitt lymphoma Overexpression of c-MYC, IGH (overexpression of proto-oncogene M). You get "starry sky".
42
t(14;18)
Follicular lymphoma Overexpression of BCL2 (anti-apoptosis). results in immortality of B-lymphocytes
43
t(15;17)
Acute myeloid leukemia PML and RARA genes
44
t(11;14)
Mantle cell lymphoma Cyclin D1 and IGH genes generalized non-tender lymphadenopathy in elderly male patient
45
t(11;22)
Ewing Sarcoma FLI1 and EWSR1 genes "X-ray tibia, onion-skin pattern, round-dark blue nuclei"
46
Presence of _____ in >90% of tumors
Telomerase
47
what skin condition leads to squamous cell carcinoma of skin?
actinic (solar) keratosis
48
what precancerous condition in the oral cavity leads to oral squamous cell carcinoma?
oral leukoplakia
49
what cancer is associated with the bronchial mucosa?
squamous cell carcinoma of lung. The precursor lesion is squamous metaplasia --> dysplasia
50
tubular/villous adenoma can lead to what cancer
adenocarcinoma of colon
51
endometrial hyperplasia can lead to?
adenocarcinoma of endometrium
52
a serous borderline tumor of ovary can lead to what?
serous papillary cystadenocarcinoma of ovary
53
inherited AR syndromes of defective DNA repair (4)
xeroderma pigmentosa ataxia telangiectasia bloom syndrome fanconi anemia
54
familial cancers (2)
breast and ovarian
55
what are the 5 categories of oncogenes?
1. GF (ex: PDGF, FGF) 2. GF receptors (ex: EGF receptor) 3. Signal transducers (ex: RAS, B-catenin) 4. Cell cycle regulators (Cyclin D, CDK4, Cyclin E) 5. transcription factor (i.e. C-MYC or N-MYC)
56
Point mutaiton of K-RAS causes ____
colon, lung and pancreatic cancers
57
point mutation of H-RAS causes ____
bladder and kidney tumors
58
Point mutaiton of N-RAS causes ____
melanomas, hematologic malignancies
59
List 4 growth factors?
PDGF-beta FGF TGF-alpha HGF
60
List 4 GF receptors?
ERBB2/HER RET PDGFRB KIT
61
List 3 signal transducers?
RAS (K, H, and N) ABL (non-receptor tyrosine kinase) BRAF (RAS)
62
List 2 transcriptional activators?
MYC | n-MYC
63
List 2 cell cycle regulators?
CCNDA1 | CDK4
64
what proto-oncogene causes mantle cell lymphoma?
CCND1
65
what proto-oncogene causes melanoma?
CDK4
66
point mutation in BRAF leads to ?
melanoma
67
point mutation in RET leads to?
MEN 2a and B familial medullary thyroid carcinoma
68
point mutation in KRAS leads to? (kristen rat sarcoma viral oncogene homolog)
pancreas and colon cancer
69
RAS proto-oncogene MOA
When RAS is bound to GDP it is "OFF" GF binds, GDP gets removed --> RAS-GTP = "active" and can send message to nucleus. "GAP" GTPase associated protein helps shut down active form of RAS by converting back to inactivated RAS-GDP (cuts away phosphate). in a mutant RAS, phosphate cannot be removed from active RAS by GAP.
70
APC function? associated cancer?
prevents nuclear transcription. Tumore supressor gene. familial polyposis coli (inherited mutation) and sporadic colon cancer (somatic mutation)
71
BRAC1 and BRCA2 function? associated cancer?
regulated DNA repair breast and ovarian cancer
72
RB function? associated cancer?
inhibits G1 to S retinoblastoma and osteogenic sarcoma
73
NF-1 function? associated cancer?
encodes neurobromin 1 = GTPase that acts as negative regulator of RAS neurofibromatosis type I
74
NF-2 function? associated cancer?
cytoskeleton protein involved in contact inhibition Neurofibromatosis type II- bilateral Schawannoma of acoustic nerve (hearing disturbances)
75
P53 function? associated cancer?
inhibits G1 to S, repairs DNA, activates BAX (initiates apoptosis) 50% of all cancers Li-Fraumeni Oncogenesis in HPV
76
VHL function? associated cancer?
ubiquitin-ligase complex and hypoxia inducible factor 1a (HIF1a) Von Hippel Lindau disease, hereditary renal cell carcinoma, pheochromocytoma and renal cysts
77
PTEN function? associated cancer?
regulates nuclear transcription cowden syndrome, CARCINOMA OF ENDOMETRIUM, breast and thyroid
78
WT1 function? associated cancer?
Transcriptional activator of genes invovled in normal development of genitorurinary tissue Wilms' tumor
79
what is the main gene involved in neuroblastoma?
N-MYC
80
What is Trastumuzab (Herceptin) associated with?
it is monoclonoal Ab against Her-2/Neu for Breast cancer
81
What is the MOA of APC?
normal function: down-regulates Beta-Catenin and prevents its accumulation. when APC is lost: B- catenin increases and it travels to nucleus where ther eis continuas WNT signaling causing FAP non-familial colorectal Cancer and sporadic adenoma
82
What is E-Cadherin?
it is a cell adhesion molecule that keeps eepithelial cells attached to each other. for tumor to spread locally and metastasize it must detach. associated with AD familial gastric carcinoma and sporadic carcinomas.
83
What is CDKN2A? (cycklin dependent kinase inhibitor 2A?
encodes 2 tumor suppressor genes (P16INK4a and ARF) associated with AD famililal melanoma
84
what is RB?
tumor suppressor that inhibits movement from G1 to S phase
85
What is RB associated with?
retinoblastoma, osteogenic sarcoma, soft tissue carcinoma
86
What is the MOA of RB?
RB "holds" E2F = "hypophosphorylated state" and cell replication is preventated (i.e. cell can't move from G1 to S). RB gets phosphorylated by cyclin D/CDK4 which then releases E2F. If RB gets mutated, E2F is free and cells can easily go from G1 to S and cause tumor.
87
What is Knudson's 2 hit hypothesis
Both alleles of RB locus must be inactivaed. 40% of retinoblastoma are familial 1st hit = all somatic cells of body (one defective copy is inherited from affected parent and other copy is normal) 2nd hit =retinal cells (somatic mutation --> loss of normal RB gene --> retinoblastoma) 60% cases sporadic cells homozygouse for mutant RB --> cancer Recessive --> heterozygous cells are normal
88
P53 MOA
inhibits G1 to S, repairs DNA and activates BAX.
89
how many copies of the P53 must be knocked out for tumor formation?
both
90
Li-Fraumeni syndrome
increased risk of carcinomas/sarcomas-- inherited p53 mutation
91
what causes oncogenesis in HPV?
viral proteins E6 and E7 | bind to inhibit RB and p53
92
MOA of BCL-2?
stabilizes mitochondrial membrane so cytochome C can't be released. If it is inhibited, cytochrome C can leak out of mitochondria and activate apoptosis. Translocation 14:18 overexpresses BCL-2 which prevents apoptosis of B cells and prevents apoptosis of B cells (B cell lymphoma) follicular lymphoma.
93
Telomerase
limitless replicative potential. Normal somatic cells have 60 to 70 doublings. telomerase is in over 90% tumors

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